Enhanced bone regeneration via endochondral ossification using Exendin-4-modified mesenchymal stem cells  

作　　者：Zihao He Hui Li Yuanyuan Zhang Shuang Gao Kaini Liang Yiqi Su Du Wang Zhen Yang Yanan Du Dan Xing Jianhao Lin 

机构地区：[1]Arthritis Clinic&Research Center,Peking University People’s Hospital,Peking University,Beijing,100044,China [2]Arthritis Institute,Peking University,Beijing,100044,China [3]Department of Biomedical Engineering,School of Medicine,Tsinghua-Peking Center for Life Sciences,MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology,Tsinghua University,Beijing,100084,China

出　　处：《Bioactive Materials》2024年第4期98-111,共14页生物活性材料（英文）

基　　金：funded by grants from Natural Science Foundation of Beijing Municipality(7212118,L222087,and L232094);the National Natural Science Foundation of China(81973606,82272538,82302776);Peking University Medicine Sailing Program for Young Scholars’Scientific&Technological Innovation(BMU2023YFJHPY010);Peking University People’s Hospital Scientific Research Development Funds(RDJP2022-04,RDGS2023-04 and RDX2023-12).

摘　　要：Nonunions and delayed unions pose significant challenges in orthopedic treatment,with current therapies often proving inadequate.Bone tissue engineering(BTE),particularly through endochondral ossification(ECO),emerges as a promising strategy for addressing critical bone defects.This study introduces mesenchymal stem cells overexpressing Exendin-4(MSC-E4),designed to modulate bone remodeling via their autocrine and paracrine functions.We established a type I collagen(Col-I)sponge-based in vitro model that effectively recapitulates the ECO pathway.MSC-E4 demonstrated superior chondrogenic and hypertrophic differentiation and enhanced the ECO cell fate in single-cell sequencing analysis.Furthermore,MSC-E4 encapsulated in microscaffold,effectively facilitated bone regeneration in a rat calvarial defect model,underscoring its potential as a therapeutic agent for bone regeneration.Our findings advocate for MSC-E4 within a BTE framework as a novel and potent approach for treating significant bone defects,leveraging the intrinsic ECO process.

关 键 词：Mesenchymal stem cells EXENDIN-4 Endochondral ossification Bone tissue engenieering Regenerative medicine NONUNION Genetic engineering 

分 类 号：R68[医药卫生—骨科学]